REEP2

protein-coding

receptor accessory protein 2, the group of Receptor accessory proteins

Gene summary

This gene encodes a member of the receptor expression enhancing protein family. Studies of a related gene in mouse suggest that the encoded protein is found in the cell membrane and enhances the function of sweet taste receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

Previous symbols:

C5orf19

MANE transcript

NM_001271803.2

Inheritance

AR, AD, SD

ClinVar variants

P:7U:63B:40

Top phenotype

Spastic paraplegia 72A, autosomal dominant; Spastic paraplegia 72B, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr5:138,439,057-138,446,969

External References & Databases

Ensembl (ENSG00000132563)

Transcript & Mutation Effects

hg38 • Region Span ~7.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019064

Submitter: Ambry Genetics

hereditary spastic paraplegia 72SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014282

Submitter: Orphanet

hereditary spastic paraplegia 72MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014282

Submitter: Ambry Genetics

hereditary spastic paraplegia 72STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014282

Submitter: Labcorp Genetics (formerly Invitae)

hereditary spastic paraplegia 72MODERATE

Inheritance Pattern: SD

Disease ID:MONDO:0014282

Submitter: Ambry Genetics

hereditary spastic paraplegia 72STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014282

Submitter: PanelApp Australia

hereditary spastic paraplegia 72STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014282

Submitter: Labcorp Genetics (formerly Invitae)

spastic paraplegia 72b, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957958

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spastic paraplegia 72A, autosomal dominant; Spastic paraplegia 72B, autosomal recessiveAD/AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24388663

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to REEP2 variants in ClinVar

8 Conditions Cataloged

Hereditary spastic paraplegia 72Total: 113

Inborn genetic diseasesTotal: 28

not providedTotal: 12

not specifiedTotal: 7

REEP2-related disorderTotal: 5

Spastic paraplegia 72b, autosomal recessiveTotal: 4

Hereditary spastic paraplegia 5ATotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001271803.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	37 clinvar	1 clinvar	39
missense	3 clinvar	1 clinvar	58 clinvar	2 clinvar		64
nonsense		2 clinvar	2 clinvar			4
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	3	4	63	39	1	110

Highest pathogenic variant AF is 0.0000018593673

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001271803.2	RefSeq	NP_001258732.1	8	MANE Select
ENST00000378339.7	Ensembl	ENSP00000367590.2	8	MANE Select
NM_016606.4	RefSeq	NP_057690.2	8	Standard
ENST00000254901.10	Ensembl	ENSP00000254901.5	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Olfactory Signaling Pathway
G alpha (s) signalling events
GPCR downstream signalling

Biological Process

regulation of intracellular transport
protein transport into membrane raft
sensory perception of bitter taste
sensory perception of sweet taste
endoplasmic reticulum tubular network organization

Molecular Function

taste receptor binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
cytoplasmic microtubule
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254901
Coding exons: 8
Length: 7953
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125741
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.64	103	161	0.638	0.0000102	1629
Missense (PolyPhen)		18	50.896	0.35367		559
Synonymous	0.520	65	70.6	0.921	0.00000506	511
Loss of Function	2.74	3	14.1	0.212	7.72e-7	156

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for endoplasmic reticulum (ER) network formation, shaping and remodeling. May enhance the cell surface expression of odorant receptors (By similarity). {ECO:0000250, ECO:0000269|PubMed:24388663}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.129
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium